Attempts to develop new therapies for SLE continue. Investigations include manipulation of T and B cell function in NZB/NZW mice, studies of immune tolerance to DNA in the mice, and prospective studies of patients receiving hydralazine therapy. T cell function was reduced in B/W mice by administration of anti-thymocyte globulin, which accelerated :nti-DNA function and nephritis. Attempts to produce similar results with another T cell suppressor, Niridazole, were unsuccessful. Attempts to improve T cell function by administration of thymosin are in progress; preliminary in vivo studies show little effect on the immune response. Studies of the effects of thymosin on in vitro lymphocyte response to T and B mitogens in patients with active SLE are also in progress. Reduction of B cell function by administration of L-asparaginase resulted in reduced antibodies to DNA, SRBC and SSS III as well as significant delay of proteinuria; the benefits of L-asparaginase were limited by the development of inactivating antibodies. Further tolerance studies showed that repeated administration of sDNA-poly-D lysine to newborn NZB/NZW mice induces immune tolerance which is hepten-specific and more effective in reducing IgM antibodies than IgG. Experiments to determine T and B cell participation in this tolerance are in progress. Patients receiving hydralazine (white and black, slow and fast acetylators) are being followed prospectively with measurement of antibodies to hydralazine and DNA at 3 month intervals to establish the prognositic significance of these tests. BIBLIOGRAPHIC REFERENCES: Hahn, B.H., Knotts, L., Ng, M., and Hamilton, T. R. Influence of cyclophosphamide and other immunosuppressive drugs on immune disorders and neoplasia in NZB/NZW mice. Arthritis Rheum. 18:145, 1975. Hahn, B.H., Kantor, O.S., and Osterland, C.K. Azathioprine plus prednisone compared with prednisone alone in the treatment of systemic lupus erythematosus. Ann Intern Med 83:497, 1975.